• The Korean Journal of Physiology and Pharmacology
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• v.4 no.6
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• pp.427-437
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• 2000

The early studies of cardiac and smooth muscle cells provided evidence for two different calcium channels, the L-type (also called high-voltage activated [HVA]) and T-type (low-voltage activated [LVA]). These calcium channels provided calcium for muscle contractions and pace-making activities. As might be expected, the number of different calcium channels increased when researchers studied neurons and the identification of the neuronal calcium channels has proven to be much more difficult than with the muscle calcium channels. There are two reasons for this difficulty; (1) a larger number of different calcium channels in neurons and (2) many of the different calcium channels have similar kinetic properties. This review uses the N-type calcium channel to illustrate the difficulties in identifying and characterizing calcium channels in neurons. It shows that the discovery of toxins that can specifically block single calcium channel types has made it possible to easily and rapidly discern the physiological roles of the different calcium channels in the neuron, Without these toxins it is unlikely that progress would have been as rapid.

• Molecules and Cells
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• v.22 no.1
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• pp.51-57
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• 2006

Haloperidol is a classical neuroleptic drug that is still in clinical use and can lead to abnormal motor activity following repeated administration. However, there is little knowledge of how it triggers neuronal impairment. In this study, we report that it induced calcium ion influx via L-type calcium channels and that the elevation of calcium ions induced by haloperidol appeared to render hippocampal cells more susceptible to oxidative stress. Indeed, the level of cytotoxic reactive oxygen species (ROS) and the expression of pro-apoptotic Bax increased in response to oxidative stress in haloperidol-treated cells, and these effects were inhibited by verapamil, a specific L-type calcium channel blocker, but not by the T-type calcium channel blocker, mibefradil. These findings indicate that haloperidol induces calcium ion influx via L-type calcium channels and that this calcium influx influences neuronal fate.

• Biomolecules & Therapeutics
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• v.26 no.5
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• pp.439-445
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• 2018

T-type calcium channels are low voltage-activated calcium channels that evoke small and transient calcium currents. Recently, T-type calcium channels have been implicated in neurodevelopmental disorders such as autism spectrum disorder and neural tube defects. However, their function during embryonic development is largely unknown. Here, we investigated the function and expression of T-type calcium channels in embryonic neural progenitor cells (NPCs). First, we compared the expression of T-type calcium channel subtypes (CaV3.1, 3.2, and 3.3) in NPCs and differentiated neural cells (neurons and astrocytes). We detected all subtypes in neurons but not in astrocytes. In NPCs, CaV3.1 was the dominant subtype, whereas CaV3.2 was weakly expressed, and CaV3.3 was not detected. Next, we determined CaV3.1 expression levels in the cortex during early brain development. Expression levels of CaV3.1 in the embryonic period were transiently decreased during the perinatal period and increased at postnatal day 11. We then pharmacologically blocked T-type calcium channels to determine the effects in neuronal cells. The blockade of T-type calcium channels reduced cell viability, and induced apoptotic cell death in NPCs but not in differentiated astrocytes. Furthermore, blocking T-type calcium channels rapidly reduced AKT-phosphorylation (Ser473) and $GSK3{\beta}$-phosphorylation (Ser9). Our results suggest that T-type calcium channels play essential roles in maintaining NPC viability, and T-type calcium channel blockers are toxic to embryonic neural cells, and may potentially be responsible for neurodevelopmental disorders.

• Journal of Nutrition and Health
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• v.29 no.5
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• pp.480-488
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• 1996

This study was performed to investigate the effect of various types of calcium sources on calcium and bone metabolism. Sprague-Dawley male rats weighing approximately 89.3g were divided into 4 groups and fed experimental diets containing 0.5% calcium for 5 weeks. Four different calcium salts were used for the study : calcium phosphate, calcium lactate, calcium gluconate, and calcium carbonate. Food intake showed no significant difference n accordance with the type of calcium salt, but bo요 weight gain and food efficiency were lower in calcium gluconate and calcium carbonate groups. There was significant differences in liver, thymus and epididymal fat pad weight with the of calcium salt ; the calcium gluconate group showed lower values compared to the other groups. Femur and scapular length were higher in calcium lactate and calcium carbonate groups. Wet weight, dry weight, and density of the femur tended to be lower in the calcium gluconate group than the other groups, but this difference was not statistically significant. The calcium content of the other groups. The calcium gluconate group showed higher urinary calcium and lower calcium absorption and balance. In conclusion, calcium and bone metabolism were different according to the type of calcium sources consumed.

• Preventive Nutrition and Food Science
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• v.7 no.1
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• pp.88-94
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• 2002

The purpose of this study was to identify factors influencing the consumption of calcium-rich foods among adolescents. A total of 96 adolescents divided into twelve focus groups were investigated during April to May 2000 in Busan. Focus group discussions were audio-taped, transcribed and analyzed using a grounded theory approach. Key factors influencing the consumption of calcium-rich foods were taste, food type, body image, and family. Motivators among the factors were taste, flood type, body image, health, family and perception, and barriers were taste, flood type, location, friends, price, weather and lactose intolerance. Taste, flood type, location and weather were found to be both motivators and barriers of consumption of calcium-rich floods according to circumstances. Some of these factors varied in importance by gender and age. Younger adolescents were more strongly influenced by taste and family than older ones. Older adolescents were strongly influenced by body image, convenience and perception. These findings could be used as a guideline for adolescents to consume calcium-rich foods.

• Journal of Life Science
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• v.25 no.2
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• pp.231-236
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• 2015

Angiotensin II (AngII) is an essential hormone that affects vascular physiology. For example, stimulation of vascular smooth muscle cells (VSMCs) rapidly induces vasoconstriction and results in the up-regulation of blood pressure. Chronic stimulation of VSMCs with AngII also results in hypertrophy. In this study, we confirmed an involvement of phosphatidylinositol 3-kinase (PI3K)-dependent calcium mobilization in AngII-induced generation of reactive oxygen species (ROS). Stimulation of rat aortic smooth muscle cells (RASMCs) with AngII significantly induced the generation of ROS in a dose- and time-dependent manner. AngII-induced generation of ROS was completely abolished by pharmacological inhibition of PI3K (with LY294002), but inhibition of the ERK signaling pathway had no effect. AngII-induced calcium mobilization was completely blocked by inhibition of PI3K, whereas inhibition of the ERK signaling pathway by PD98059 was ineffective. Depletion of extracellular calcium or inhibition of the L-type calcium channel by nifedipine completely blocked AngII-induced calcium mobilization. Depletion of extracellular calcium by EGTA and incubation of RASMCs with calcium-free medium both significantly blocked AngII-induced ROS generation. Inhibition of the L-type calcium channel also significantly blocked AngII-induced ROS generation. These results suggest that AngII-induced ROS generation is regulated by calcium mobilization, which, in turn, is modulated by a PI3K/L-type calcium channel signaling pathway.

• The Korean Journal of Ecology
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• v.21 no.1
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• pp.47-63
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• 1998

In order to compare species-specific calcium metabolism, we collected 127 species belonging to 40 different families grown on various habitats including saline, limestone, wetland during the 1996 vegetation period, and analyzed their inorganic ion contents. Plants investigated were divided into 5 groups according to their physiological properties: 1) Chenopodiaceae, Aizoaceae, Caryophyllaceae, Portulacaceae and Phytolaccaceae of Centrospermales and Polygonaceae (Polygonales had a little water-soluble $Ca^{2+}$ but contained high contents of insoluble $Ca^{2+}$ particularly as Ca-oxalate (Chenopodiaceae type), 2) Some plant species such as Rosaceae produced oxalate in amounts insufficient to precipitate all incoming $Ca^{2+}$ and thus contained a surplus of dissolved $Ca^{2+}$ (Rosaceae type), 3) The contents of water-soluble $Ca^{2+}$ in plant species of Crassulaceae. Plantaginaceae, Asclepiadaceae, and Zygophyllaceae were equal to or greater than those of K ($K/Ca{\leq}1$; Crassulaceae type), and 4) K/Ca ratios of Compositae were significantly fluctuated depending on species and soil $Ca^{2+}$ level of their habitats (Compositae type). 5) Certain monocots (Gramineae, Cyperaceae, Juncaceae), in contrast to the dicotyledonous plant families mentioned above, showed a very distinct type of calcium metabolism, that is, the K/Ca ratios of 8~10 were maintained indifferently in the species and their habitat types (Graminae type). These results plants within the same taxon have similar physiological aspects as weel as morphological attributes. To understand calcium metabolism of certain plant species, therefore, it is desirable to approach on the basis of physiological concept (calciotroph or calciophobe) rather than the ecological one (calcicole or calcifuge).

• Biomolecules & Therapeutics
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• v.28 no.5
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• pp.389-396
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• 2020

Valproic acid is a clinically used mood stabilizer and antiepileptic drug. Valproic acid has been suggested as a teratogen associated with the manifestation of neurodevelopmental disorders, such as fetal valproate syndrome and autism spectrum disorders, when taken during specific time window of pregnancy. Previous studies proposed that prenatal exposure to valproic acid induces abnormal proliferation and differentiation of neural progenitor cells, presumably by inhibiting histone deacetylase and releasing the condensed chromatin structure. Here, we found valproic acid up-regulates the transcription of T-type calcium channels by inhibiting histone deacetylase in neural progenitor cells. The pharmacological blockade of T-type calcium channels prevented the increased proliferation of neural progenitor cells induced by valproic acid. Differentiated neural cells from neural progenitor cells treated with valproic acid displayed increased levels of calcium influx in response to potassium chloride-induced depolarization. These results suggest that prenatal exposure to valproic acid up-regulates T-type calcium channels, which may contribute to increased proliferation of neural progenitor cells by inducing an abnormal calcium response and underlie the pathogenesis of neurodevelopmental disorders.

• The Korean Journal of Physiology and Pharmacology
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• v.10 no.5
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• pp.255-261
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• 2006

Melittin-induced nociceptive responses are mediated by selective activation of capsaicin-sensitive primary afferent fibers and are modulated by excitatory amino acid receptor, cyclooxygenase, protein kinase C and serotonin receptor. The present study was undertaken to investigate the peripheral and spinal actions of voltage-gated calcium channel antagonists on melittin-induced nociceptive responses. Changes in mechanical threshold and number of flinchings were measured after intraplantar (i.pl.) injection of melittin $(30\;{\mu}g/paw)$ into mid-plantar area of hindpaw. L-type calcium channel antagonists, verapamil [intrathecal (i.t.), 6 or $12\;{\mu}g$; i.pl.,100 & $200\;{\mu}g$; i.p., 10 or 30 mg], N-type calcium channel blocker, ${\omega}-conotoxin$ GVIA (i.t., 0.1 or $0.5\;{\mu}g$; i.pl., $5\;{\mu}g$) and P-type calcium channel antagonist, ${\omega}-agatoxin$ IVA (i.t., $0.5\;{\mu}g$; i.pl., $5\;{\mu}g$) were administered 20 min before or 60 min after i.pl. injection of melittin. Intraplantar pre-treatment and i.t. pre- or post-treatment of verapamil and ${\omega}-conotoxin$ GVIA dose-dependently attenuated the reduction of mechanical threshold, and melittin-induced flinchings were inhibited by i.pl. or i.t. pre-treatment of both antagonists. P-type calcium channel blocker, ${\omega}-agatoxin$ IVA, had significant inhibitory action on flinching behaviors, but had a limited effect on melittin-induced decrease in mechanical threshold. These experimental findings suggest that verapamil and ${\omega}-conotoxin$ GVIA can inhibit the development and maintenance of melittin-induced nociceptive responses.

• Proceedings of the Korean Biophysical Society Conference
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• 2003.06a
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• pp.47-47
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• 2003

The presenilin 1 (PS1) or PS2 is an essential component of the ${\gamma}$-secretase complex, which mediates the intramembrane proteolysis of selected type-I membrane, including the ${\beta}$-amyloid precursor protein (APP) to yield A${\beta}$. Familial Alzheimer's disease (FAD)-associated mutations in presenilins give rise to an increased production of a highly amyloidogenic A${\beta}$42. In addition to their well-documented proteolytic function, the presenilins play a role in calcium signaling. We have previously reported that presenilin FAD mutations cause highly consistent alterations in intracellular calcium signaling pathways, which include deficits in capacitative calcium entry (CCE), the refilling mechanism for depleted internal calcium stores. However, molecular basis for the presenilin-mediated modulation of CCE remains to be elucidated. In the present study, whole-cell patch clamp method was used to identify a specific calcium-permeable ion channel current(s) that is responsible for the CCE deficits associated with FAD-linked PS1 mutants. Unexpectedly, both voltage-activated and conventional store depletion-activated calcium currents I(CRAC), were absent in HEK293 cells, which were stably transfected either with wild-type or FAD mutant (L286V, M146L, and delta E9) forms of PS1. Recently, magnesium-nucleotide-regulated metal cation current, or I(MagNum), has been described and appears to share many common properties with I(CRAC) including calcium permeability and inhibitor sensitivity (e.g. 2-APB). We have detected I(MagNum) in all 293 cells tested. Interestingly, FAD mutant 293 cells developed only about half of currents compared to PS1 wild type cells.